White Rose University Consortium logo
University of Leeds logo University of Sheffield logo York University logo

Regulation of neutrophil senescence by microRNAs

Ward, J.R., Heath, P.R., Catto, J.W., Whyte, M.K.B., Milo, M. and Renshaw, S.A. (2011) Regulation of neutrophil senescence by microRNAs. Plos One, 6 (1). Art no.e15810. ISSN 1932-6203

Full text available as:
[img]
Preview
Text
Renshaw_Regulation.pdf

Download (439Kb)

Abstract

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease.

Item Type: Article
Copyright, Publisher and Additional Information: © 2011 Ward et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Polymorphonuclear Leukocytes; Hepatocellular-Carcinoma; Differential Expression; Gene-Expression; Cell-Death; Apoptosis; Cancer; Survival; Inflammation; Activation
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield) > Department of Infection & Immunity
The University of Sheffield > Faculty of Science (Sheffield) > School of Biological Sciences (Sheffield) > Department of Biomedical Science (Sheffield) > Centre for Developmental Genetics (Sheffield)
The University of Sheffield > University of Sheffield Research Centres and Institutes > Centre for Developmental Genetics (Sheffield)

The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology (Sheffield)
Depositing User: Miss Anthea Tucker
Date Deposited: 07 Mar 2011 16:14
Last Modified: 04 Jun 2014 18:19
Published Version: http://dx.doi.org/10.1371/journal.pone.0015810
Status: Published
Publisher: Public Library Science
Refereed: Yes
Identification Number: 10.1371/journal.pone.0015810
URI: http://eprints.whiterose.ac.uk/id/eprint/42899

Actions (repository staff only: login required)